Fibronectin (FN) is a major matrix protein involved in multiple processes. Little is known about how adhesion to FN affects the translational machinery. We show that in fibroblasts adhesion to FN triggers translation through the coordinated regulation of eukaryotic initiation factors (elFs) 4F and 2 and is impaired by blocking β1 integrin engagement. FN-stimulated translation has unique properties: (i) it is highly sensitive to the inhibition of phosphatidylinositol 3-kinase (PI3K), but not to the inhibition of mammalian target of rapamycin, downstream of PI3K; (ii) there is no synergy between serum-stimulated translation and FN-dependent translation; (iii) FN-dependent translation, unlike growth factor-stimulated translation, does not lead to increased translocation of 5′ terminal oligopyrimidine tract mRNAs to polysomes; and (iv) cells devoid of attachment to matrix show an impairment of initiation of translation accompanied by phosphorylation of elF2α, which cannot be reverted by active PI3K. These findings indicate that integrins may recruit the translational machinery in a unique way and that FN-dependent translation cannot be blocked by mammalian target of rapamycin inhibition.

Fibronectin controls cap-dependent translation through β1 integrin and eukaryotic initiation factors 4 and 2 coordinated pathways / C. Gorrini, F. Loreni, V. Gandin, L.A. Sala, N. Sonenberg, P.C. Marchisio, S. Biffo. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 102:26(2005), pp. 9200-9205. [10.1073/pnas.0409513102]

Fibronectin controls cap-dependent translation through β1 integrin and eukaryotic initiation factors 4 and 2 coordinated pathways

C. Gorrini
Primo
;
V. Gandin;L.A. Sala;S. Biffo
Ultimo
2005

Abstract

Fibronectin (FN) is a major matrix protein involved in multiple processes. Little is known about how adhesion to FN affects the translational machinery. We show that in fibroblasts adhesion to FN triggers translation through the coordinated regulation of eukaryotic initiation factors (elFs) 4F and 2 and is impaired by blocking β1 integrin engagement. FN-stimulated translation has unique properties: (i) it is highly sensitive to the inhibition of phosphatidylinositol 3-kinase (PI3K), but not to the inhibition of mammalian target of rapamycin, downstream of PI3K; (ii) there is no synergy between serum-stimulated translation and FN-dependent translation; (iii) FN-dependent translation, unlike growth factor-stimulated translation, does not lead to increased translocation of 5′ terminal oligopyrimidine tract mRNAs to polysomes; and (iv) cells devoid of attachment to matrix show an impairment of initiation of translation accompanied by phosphorylation of elF2α, which cannot be reverted by active PI3K. These findings indicate that integrins may recruit the translational machinery in a unique way and that FN-dependent translation cannot be blocked by mammalian target of rapamycin inhibition.
Initiation; Mammalian target of rapamycin (mTOR); Terminal oligopyrimidine tract mRNAs; Animals; Antigens, CD29; Blotting, Northern; Cell Adhesion; Cell Line; Enzyme Inhibitors; Eukaryotic Initiation Factor-2; Fibroblasts; Fibronectins; Guanosine Triphosphate; Humans; Immunoblotting; Integrins; Mice; NIH 3T3 Cells; Peptide Initiation Factors; Phosphatidylinositol 3-Kinases; Phosphorylation; Polyribosomes; Protein Kinases; Protein Transport; Proteins; Pyrimidines; RNA; RNA, Messenger; TOR Serine-Threonine Kinases; Transfection; Protein Biosynthesis; Genetics; Multidisciplinary
Settore BIO/06 - Anatomia Comparata e Citologia
2005
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/492837
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